TTN non-truncating variants in DCM cohorts

TTN gene summary
Overview of TTN in DCM

The table below lists the 70 rare (MAF<0.0001 in ExAC) non-truncating TTN variants identified in a cohort of 156 DCM patients (304 patients from OMGL, 156 patients from LMM). When this rare variant frequency of 0.44870 is compared with a background population rate of 0.39200, there is a statistically significant case excess of 0.05670 (p<0.0001), which suggests that approximately of these variants may be pathogenic.


Source:      Combined (OMGL + LMM)     -     OMGL     -     LMM



No. Variant (CDS)▼ Variant (Protein) Variant Type▼ Cases (156)▼OMGL classLMM class ExAC frequency
1. c.37432C>T p.P12478Smissense 2VUS (2)0.000000
2. c.20260A>G p.Lys6754Glumissense 1VUS (1)0.000000
3. c.11450G>A p.G3817Dmissense 1VUS (1)0.000017
4. c.89947G>A p.V29983Mmissense 1VUS (1)0.000099
5. c.43019T>C p.I14340Tmissense 1VUS (1)0.000008
6. c.3469G>A p.V1157Imissense 1VUS (1)0.000041
7. c.80608C>A p.Pro26870Thrmissense 1VUS (1)0.000000
8. c.96140C>T p.T32047Mmissense 1VUS (1)0.000057
9. c.48395G>A p.R16132Hmissense 1VUS (1)0.000066
10. c.5582G>A p.R1861Hmissense 1VUS (1)0.000082
11. c.55139T>C p.I18380Tmissense 1VUS (1)0.000050
12. c.58982G>A p.G19661Dmissense 1VUS (1)0.000016
13. c.39749_39766delTTGCTCCTGAAGAGGAAA inframe 1VUS (1)0.000000
14. c.9674A>G p.N3225Smissense 1VUS (1)0.000024
15. c.68272G>A p.D22758Nmissense 1VUS (1)0.000026
16. c.1186G>A p.A396Tmissense 1VUS (1)0.000008
17. c.78980G>A p.R26327Qmissense 1VUS (1)0.000049
18. c.74527A>G p.N24843Dmissense 1VUS (1)0.000033
19. c.50647C>T p.Pro16883Sermissense 1VUS (1)0.000000
20. c.39163A>G p.Lys13055Glumissense 1VUS (1)0.000000
21. c.91478A>G p.Glu30493Glymissense 1VUS (1)0.000000
22. c.94629A>G p.I31543Mmissense 1VUS (1)0.000066
23. c.63632T>C p.Val21211Alamissense 1VUS (1)0.000000
24. c.99814C>T p.L33272Fmissense 1VUS (1)0.000009
25. c.58684A>G p.Ile19562Valmissense 1VUS (1)0.000000
26. c.105590G>A p.G35197Dmissense 1VUS (1)0.000041
27. c.15369_15371delGTT inframe 1VUS - favor pathogenic (1)0.000000
28. c.12037G>A p.Ala4013Thrmissense 1VUS (1)0.000000
29. c.6941T>C p.I2314Tmissense 1VUS (1)0.000008
30. c.20742T>A p.Phe6914Leumissense 1VUS (1)0.000000
31. c.18663A>C p.E6221Dmissense 1VUS (1)0.000099
32. c.77816A>C p.Asp25939Alamissense 1VUS (1)0.000000
33. c.22386T>G p.Asp7462Glumissense 1VUS (1)0.000000
34. c.72985A>G p.Asn24329Aspmissense 1VUS (1)0.000000
35. c.28754A>C p.Glu9585Alamissense 1VUS (1)0.000000
36. c.70181C>T p.T23394Mmissense 1VUS (1)0.000024
37. c.85195G>A p.E28399Kmissense 1VUS (1)0.000016
38. c.57415A>C p.Ile19139Leumissense 1VUS (1)0.000000
39. c.96286G>A p.A32096Tmissense 1VUS (1)0.000066
40. c.54091A>G p.S18031Gmissense 1VUS (1)0.000008
41. c.93472G>C p.Asp31158Hismissense 1VUS (1)0.000000
42. c.62290G>C p.Glu20764Glnmissense 1VUS (1)0.000000
43. c.89766G>C p.Lys29922Asnmissense 1VUS (1)0.000000
44. c.107285G>A p.R35762Qmissense 1VUS (1)0.000033
45. c.64903C>T p.R21635Cmissense 1VUS (1)0.000024
46. c.6029A>G p.Y2010Cmissense 1VUS (1)0.000008
47. c.11140A>G p.Ile3714Valmissense 1VUS (1)0.000000
48. c.26765G>A p.Arg8922Glnmissense 1VUS (1)0.000000
49. c.19015T>C p.Tyr6339Hismissense 1VUS (1)0.000000
50. c.24344G>A p.S8115Nmissense 1VUS (1)0.000083
51. c.72488G>A p.R24163Hmissense 1VUS (1)0.000054
52. c.84523T>C p.Trp28175Argmissense 1VUS (1)0.000000
53. c.2605A>T p.T869Smissense 1VUS (1)0.000041
54. c.47887A>G p.M15963Vmissense 1VUS (1)0.000033
55. c.98296G>T p.D32766Ymissense 1VUS (1)0.000008
56. c.54685G>A p.V18229Mmissense 1VUS (1)0.000091
57. c.102638A>G p.N34213Smissense 1VUS (1)0.000008
58. c.58705G>A p.D19569Nmissense 1VUS (1)0.000017
59. c.105630A>C p.Gln35210Hismissense 1VUS (1)0.000000
60. c.98243G>A p.R32748Hmissense 1VUS (1)0.000066
61. c.67147G>A p.G22383Rmissense 1VUS (1)0.000058
62. c.25046C>G p.A8349Gmissense 1VUS (1)0.000008
63. c.5132C>T p.S1711Fmissense 1VUS (1)0.000016
64. c.99434G>A p.R33145Qmissense 1VUS (1)0.000033
65. c.54167G>A p.R18056Qmissense 1VUS (1)0.000026
66. c.102428T>C p.M34143Tmissense 1VUS (1)0.000074
67. c.93968C>T p.A31323Vmissense 1VUS (1)0.000057
68. c.62780G>A p.R20927Hmissense 1VUS (1)0.000008
69. c.6478A>G p.T2160Amissense 1VUS (1)0.000016

References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.